Dietary fatty acids differentially regulate production of TNF-α and IL-10 by murine 3T3-L1 adipocytes

被引:120
作者
Bradley, Richard L. [1 ]
Fisher, FFolliott M. [1 ]
Maratos-Flier, Eleftheria [1 ]
机构
[1] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med,Div Endocrinol, Boston, MA 02215 USA
关键词
D O I
10.1038/oby.2008.39
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective: Obesity correlates with increased production of adipocyte-derived cytokines, which may contribute to a chronic subclinical inflammation seen in obese individuals. This study evaluated the ability of specific fatty acids to modulate production of the proinflammatory cytokine, tumor necrosis factor-alpha (TNF-alpha), and the anti-inflammatory cytokine, interleukin-10 (IL-10), in murine 3T3-L1 adipocytes. Effects on nuclear factor-kappa B (NF-kappa B), a key transcriptional activator of the inflammatory cascade, and suppressor of cytokine signaling 3 (SOCS-3), a negative regulator of cytokine signaling, were also determined. Methods and Procedures: Adipocytes were incubated for 24 and 48 h with and without 50 or 500 mu mol/l of palmitic acid, oleic acid, or docosahexaenoic acid, (DHA). Effects on gene expression and protein secretion of TNF-alpha and IL-10 were determined using real-time PCR and a murine multipex RIA kit. SOCS-3 expression was determined by northern blotting and NF-kappa B binding activity was assessed using a commercially available assay. Results: Adipocytes treated for 24 h with palmitic acid exhibited a 70% increase in TNF-alpha production and up to a 75% decrease in IL-10 production, relative to untreated cells. In contrast, DHA treatment had no effect on TNF-alpha, but increased IL-10 production twofold. No effect of oleic acid was seen on either TNF-alpha or IL-10 production. Similar results were obtained during a 48-h incubation. Furthermore, NF-kappa B DNA-binding activity increased fourfold in response to palmitic acid and decreased 60% in response to DHA. Expression of SOCS-3 increased twofold in DHA-treated cells. Discussion: In aggregate, these results suggest that dietary fatty acids act directly on adipocytes to modulate cytokine production. As circulating fatty acids levels are chronically elevated in obese individuals, this effect may account in part for obesity-associated inflammation.
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收藏
页码:938 / 944
页数:7
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